Numerous materials and methods have been developed for providing antimicrobial properties to medical items, consumer articles and food packaging. Nearly all of the methods thus far developed rely on the release of bacteriocides or bacteriostats to kill unwanted microbes such as bacteria, viruses, yeast, etc. In order for an antimicrobial article to be effective against harmful micro-organisms, the antimicrobial compound must come in direct contact with micro-organisms present in the surrounding environment, such as food, liquid nutrient or biological fluid. This creates a problem in that the surrounding environment may become contaminated with the antimicrobial compounds, which may potentially alter the color or taste of items such as beverages and foodstuffs, and in the worst case may be harmful to the persons using or consuming those items. The wide spread use of antimicrobial materials may cause further problems in that disposal of the items containing these materials cannot be accomplished without impacting the biological health of the landfill or other site of disposal; and further the antimicrobial compounds may leach into surrounding rivers, lakes and water supplies. The wide spread use of antimicrobial materials may cause yet further problems in that micro-organisms may develop resistance to these materials and new infectious microbes and new diseases may develop.
Small concentrations of metal-ions may play an important role in biological processes. For example, Mn, Fe, Ca, Zn, Cu and Al are essential bio-metals, and are required for most, if not all, living systems. Metal-ions play a crucial role in oxygen transport in living systems, and regulate the function of genes and replication in many cellular systems. Calcium is an important structural element in the formation of bones and other hard tissues. Mn, Cu and Fe are involved in metabolism and enzymatic processes. At high concentrations, metals may become toxic to living systems and the organism may experience disease or illness if the level cannot be controlled. As a result, the availability and concentrations of metal-ions in biological environments is a major factor in determining the abundance, growth-rate and health of plant, animal and micro-organism populations.
It has been recognized that iron is an essential biological element, and that all living organisms require iron for survival and replication. Although the occurrence and concentration of iron is relatively high on the earth's surface, the availability of “free” iron is severely limited by the extreme insolubility of iron in aqueous environments. As a result, many organisms have developed complex methods of procuring “free” iron for survival and replication. Controlling the concentration of “free’ iron in any biological system can, therefore, allow one to control the growth rates and abundance of micro-organisms. Such control can be of great use for treating sickness and disease, inhibiting bacterial growth, treating wounds, and providing for the general health of plant, animal, micro-organism and human populations. Indeed, iron “chelating” or “sequestering” drugs are used to treat iron deficiency in plants; and are used to treat diseases such as Cooley's anemia (thalassemia), sickle-cell anemia, and iron overload diseases in humans.
Metal-ions may also exist as contaminants in environments such as drinking water, beverages, food, industrial effluents and public waste waters, and radioactive waste. Methods and materials for removing such contaminants are important for cleaning the environment(s) and providing for the safety of the general public.
U.S. Pat. No. 5,217,998 to Hedlund et al. describes a method for scavenging free iron or aluminum in fluids such as physiological fluids by providing in such fluids a soluble polymer substrate having a chelator immobilized thereon. A composition is described which comprises a water-soluble conjugate comprising a pharmaceutically acceptable water-soluble polysaccharide covalently bonded to deferoxamine, a known iron chelator. The conjugate is said to be capable of reducing iron concentrations in body fluids in vivo. The iron chelator is covalently bound to a soluble polymer and thus may not be easily or readily immobilized upon a substrate.
U.S. Pat. No. 6,156,234 to Meyer-Ingold et al. describes novel wound coverings which can remove interfering factors (such as iron ions) from the wound fluid of chronic wounds. The wound coverings may comprise iron chelators covalently bonded to a substrate such as cloth or cotton bandages.
U.S. Pat. No. 5,560,929 to Hedstrand et al. describes dense star polymers or dendrimers having a highly branched interior structure and capable of associating or chelating with metal-ions. Affinity for metal ions is achieved by modifying the dense star polymers with a plurality of oxygen and nitrogen atoms.
U.S. Pat. No. 5,854,303 to Powell et al. describes a polymeric material incorporating a polyvalent cation chelating agent in an amount effective to inhibit the growth of an ocular pathogen. The polymer of the invention may consist of a plurality of monomers, which are covalently modified with an agent capable of chelating a metal-ion, such as an alpha amino carboxylate.
The materials and methods described above, while capable of sequestering metal-ions, are difficult and expensive to prepare and require a covalent linkage of the chelator or chelate-functionality to the polymer or polymeric substrate. The covalent linkage, in addition to requiring multiple steps to achieve, is problematic because it often interferes with the chelators ability to form a complex with a polyvalent cation or metal-ion. The interference is a result of the steric constraint placed upon the chelator by the covalent linkage, i.e., the chelator may no longer be free to wrap itself around the target metal-ion. Further, the covalent linkage may also eliminate one of the “arms” of the chelator and reduce its denticity, i.e, the number of bonds it forms with the target metal-ion. Further still, the linkage may eliminate the chelators ability to bind a specific target metal-ion. Since the linkage is built covalently this limits the adaptability of the method to materials which do not contain the required functionalities for attachment.
Materials and methods are needed that are able to provide immobilized metal-ion chelators that are not sterically constrained and that do not have reduced denticity with the target metal-ion. Materials are needed that are able to target and remove specific metal-ions, while leaving intact the concentrations of beneficial metal-ions. Furthermore, materials are needed that have a high capacity for metal-ions and which provide for the efficient removal of metal-ions in a cost effective manner. Materials and methods are needed for sequestering metal-ions even in extremely low concentrations and removing metal-ion contaminants to levels below 100 parts per billion (ppb) and still further below 10 ppb. Materials and methods are needed for applying immobilized metal-ion sequestrants to numerous items and articles without significantly changing their color or appearance.